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com Vol 7 June 2008 525

Review
Outcomes of epilepsy surgery in adults and children
Susan Spencer, Linda Huh
Surgery is widely accepted as an eective therapy for selected individuals with medically refractory epilepsy. Numerous
studies in the past 20 years have reported seizure freedom for at least 1 year in 5384% of patients after anteromesial
temporal lobe resections for mesial temporal lobe sclerosis, in 66100% of patients with dual pathology, in 3676% of
patients with localised neocortical epilepsy, and in 4379% of patients after hemispherectomies. Reported rates for
non-resective surgery have been less impressive in terms of seizure freedom; however, the benet is more apparent
when reported in terms of signicant seizure reductions. In this Review, we consider the outcomes of surgery in
adults and children with epilepsy and review studies of neurological and cognitive sequelae, psychiatric and
behavioural outcomes, and overall health-related quality of life.
Introduction
Up to a third of all individuals with epilepsy are
refractory to medical therapy.
1
Epilepsy surgery is now
widely accepted as an eective therapeutic option in a
selected subset of these patients.
26
Surgical procedures
for epilepsy include resection (anteromedial temporal
lobectomy, focal neocortical resection, lesional
resection, and hemispherectomy) and disconnection
procedures (corpus callosotomy and multiple subpial
transections); the stimulation procedures (vagal nerve
stimulation, responsive neurostimulation, thalamic
stimulation, and transcranial stimulation) are not
covered in this Review.
Epilepsy surgery in children is not simply an extension
of adult procedures, and additional complicating factors
must be considered, including dierent causes of
epilepsy, the detrimental eects of seizures and
antiepileptic drugs on the developing brain, and the
capacity for functional plasticity in younger patients.
Another challenge in children is that each age group
neonates, infants, children, and adolescentshas unique
surgical considerations that can dier appreciably from
one another, and from adults.
In both children and adults, seizure freedom, or
improvement of seizure control, is the desired and most
commonly reported outcome. However, other outcomes
are important to consider and assess, including
enhancement of developmental or cognitive potential,
treatment of behavioural and psychosocial di culties,
and improvement of health-related quality of life for
patients and their families. Many studies report notable
successes, including seizure freedom and improvements
in other neurological and cognitive measures, for surgery
in appropriately selected patients.
24
In this Review, we
provide a current and comprehensive overview of these
global and specic outcomes of epilepsy surgery in
children and adults.
Seizure outcomes
Methods of reporting seizure outcome are heterogeneous
among papers. Therefore, we used a well dened, widely
applicable, and clinically useful criterion for success of
surgery: namely, seizure freedom (with or without
isolated auras) for at least 1 year at last follow-up
regardless of antiepileptic medication status (Engel class
1ac,
7
ILAE classication
8
class 1, 1a, and 2, seizure-
frequency scoring system
9
03). This method circumvents
the di culties of separating patients on or o antiepileptic
medications or accounting for relapses and remissions,
which are not cited in most papers despite the usefulness
of such information. The use of seizure freedom,
however, is limited by the fact that many papers do not
account for patients lost to follow-up.
Resective surgery
Surgical resection of the seizure-generating region is
the preferred procedure. In adults, most surgical
procedures involve anteromedial temporal lobe
resection to treat mesial temporal sclerosis, whereas in
children, removal of space-occupying lesions identied
as causing the seizures is more common. Each
procedure has its own surgery-related controversies and
continues to be modied and improved in the light of
response rates and secondary outcomes. Initial
approaches to resection included anterior temporal
resection of roughly equal extent along medial and
lateral temporal structures.
10
The study of temporal lobe
tissue, informed by invasive electroencephalographic
(EEG) recordings and outcomes of surgery, revealed
that most pathology and seizure activity is located in
the medial temporal lobe. The procedure then developed
into a more or less medial amygdalohippocampal
resection, with or without some temporal polar resection
(anteromedial temporal resection).
1116
Some surgeons
used intraoperative electrocorticography to determine
the extent of temporal lobe tissue to be removed
(tailored resection), but this approach is less common
now and not proven to be entirely valid or predictive of
results, except for space-occupying lesions.
17,18
Outcome in adults
Mesial temporal lobe sclerosis is the most common
indication for surgery in adultsaccounting for up to
75% of cases in adult surgical series
19,20
and most
operations are resections of aected sclerotic medial
temporal structures with variable additional lateral
temporal lobe removal. After temporal lobe resection,
4884% of patients are seizure free
2,3,9,2140
(table 1).
Lancet Neurol 2008; 7: 52537
Yale University, School of
Medicine, New Haven, CT, USA
(S Spencer MD, L Huh MD)
Correspondence to:
Susan Spencer, Yale University,
School of Medicine,
PO box 208018, New Haven,
CT 06520-8018, USA
susan.spencer@yale.edu
For more on refractory epilepsy
see Review page 514
526 http://neurology.thelancet.com Vol 7 June 2008
Review
Systematic reviews suggest that 6670% of patients are
seizure free at short-term (<5 years) follow-up.
2,4,4143
In the
only randomised, controlled study of this operation to date,
58% of 40 patients assigned to the surgical arm were free of
seizures impairing consciousness at 1 year after surgery,
compared with 8% of those who were medically
managed.
43
Positive predictive factors for seizure freedom after
temporal lobe resection include preoperative hippocampal
sclerosis (unilateral), focal localisation of interictal
epileptiform discharges, absence of preoperative
generalised seizures, tumoural cause, and complete
resection of the lesion with or without medial
structures.
4,6,30,34,39,42
Some patients have mesial temporal
sclerosis and a lesion outside the temporal lobe; because
the sclerosis can be just as signicant a cause or contributor
to the refractory epilepsy as the lesion it might also require
resection. However, this so-called dual pathology is poorly
identied in most studies. The presence of febrile seizures,
younger age at surgery or at onset of epilepsy, and absence
of seizures in the rst postoperative week might also
predict good seizure outcome after temporal
resection.
29,30,42,43
Long-term follow-up (>5 years) studies show that 4179%

of patients remain seizure free after temporal lobe
resection (table 1),
2,9,21,23,24,34,37,40,41,44
and that 1520% of patients
have relapses after initial seizure freedom at 510 years
after surgery.
4,37,41,44
Late relapse is more common after
medial temporal resections than after extratemporal
resections.
4548
Although potential explanations for this
phenomenon, such as contralateral mesial temporal
pathology or dual pathology, have been suggested, the only
conrmed predictor for late relapse is failure to enter
remission immediately after surgery.
4,37,49
Few studies report separate outcomes of neocortical
resections in relation to specic lobe or pathology.
Between 36% and 76% of patients are seizure free after
neocortical resection.
2,19,38,5061
Operations are guided in
their extent by intraoperative pathological margins or by
electrocorticography, neither of which is clearly proven to
be preferable for predicting outcome, and the ultimate
determination might be very similar. Factors that predict
good seizure outcome include presence of a discrete
lesion on MRI, complete resection of the lesion, localised
scalp EEG ictal onset, concordant hypometabolism on
uorodeoxyglucose-PET (with lesion or localised EEG),
longer duration of epilepsy, and lack of febrile
seizures.
2,19,22,38,5061
Some studies include both adult and
paediatric patients and a mixture of causes, sometimes
with mesial temporal sclerosis (dual pathology).
In recent surgical series, 111% of patients had
reoperation for surgical failure, which is most common
after neocortical resections.
6265
Surgical failures are
attributed to incomplete resection of lesions, erroneous
identication of epileptogenic regions, generation of new
epileptogenic zones, and limited resections due to the
risk of functional impairment.
6265
Surgical resections are
usually done in the same region as the previous surgery.
After reoperation, 3957% of patients are seizure
free.
4,21,23,25,30,52,6265
Gonzalez-Martinez
65
reported 57 patients
who had repeated resections and found substrates of
cortical dysplasia and mesial temporal sclerosis to be
poor predictive factors for seizure freedom. Siegel and
colleagues
62
found that a duration of epilepsy of 5 years or
less and preoperative focal interictal epileptiform
discharges predicted good outcome.
Outcome in children
Outcome of resective surgery to treat epilepsy in children
diers from that in adults primarily because the syndromes
amenable to surgery are much more heterogeneous. In
children, cortical dysplasia (2378%) and tumours (1738%)
are the most common syndromes, with neuro cutaneous
disorders, hemispheric syndromes (Rasmussens
encephalitis, hemimegalencephaly), perinatal injury,
epileptic encephalopathies, hypothalamic hamartomas,
and mesial temporal sclerosis occurring with declining
prevalence.
19,20,6668
Despite substantial dierences in the
developmental stages of the brain, seizure outcome after
surgery seems to be similar for infancy, childhood, and
adolescence, although there is some variation with
substrate and localisation.
In paediatric temporal lobectomy series, 1340%
20,67,69,70
of
cases have mesial temporal sclerosis, and the prevalence of
829% in all surgical procedures is lower than that in
Age Follow-up
(years)
Number of
patients
Proportion seizure free after
surgery
Al-Kaylani et al
21
Adult >2 (mean 6) 150 78% (no dierence with MTS)
Alpherts et al
22
Adult 6 71 68%
Aszetely et al
23
Adult >86 (mean 122) 54 65%
Bien et al
24
Adult >2 yrs (mean 48) 148 62%
Cohen-Gadol et al
25
369 years Mean 62 years 372 79%
Dulay et al
26
>17 years 1 90 61% overall, 61% MTS, 12% MTS+
Dupont et al
27
Adult 1 110 73% (but 41% at 10 years post-op)
Gilliam et al
28
>17 years 1 196 65%
Jeong et al
29
951 years 18 months 93 84%
Jutila et al
30
1454 years >1 (mean 54) 140 56%
Kellet et al
31
Adult 1 94 48% MTS, 65% tumour
Lee et al
32
955 years 1 171 72%
Pintor et al
33
Adult 1 70 68%
Radhakrishnan et al
34
786 years >2 (mean 3.6) 175 77%
Salanova et al
35
857 years >1 (mean 7) 215 69%
Sanyal et al
36
>15 years 1 25 76% MTS, 74% lesional
So et al
9
786 years >1 184 74%
Spencer et al
37
>12 years >2 (mean 46) 297 68%
Sperling et al
38
Adult and
adolescent
2 86 56%
Wiebe et al
39
Adult 1 36 64%
Zaatreh et al
40
876 years >2 (mean 9) 68 65% (all tumoural)
MTS=mesial temporal sclerosis. MTS+=dual pathology.
Table 1: Studies of temporal lobectomy to treat epilepsy in adults
http://neurology.thelancet.com Vol 7 June 2008 527
Review
adults.
62,6668
Most paediatric mesial temporal sclerosis is in
adolescent patients, although some children less than the
age of 3 years have this pathology.
71
The rates of seizure
freedom after surgery are comparable to those in adults,
and range from 58% to 78%.
20,66,67,70,7274
Mohamed and co-
workers
72
found that bilateral mesial temporal sclerosis on
MRI or only mild unilateral sclerosis and bilateral temporal
epileptiform discharges on interictal EEG recordings
might be associated with worse outcome.
A similar proportion of paediatric neocortical resections
lead to seizure freedom as in adults, with overall freedom
from seizures in 5970% of children (6091% for
temporal and 5466% for extratemporal
resections).
19,20,66,67,70,7581
The slightly higher range is
probably a reection of a greater proportion of lesional
substrates in neocortical resections in children. Patients
who had multilobar resections had lower rates of seizure-
free outcome.
20,66,75
Children with tuberous sclerosis had
similar rates of seizure-free outcome to those with other
substrates.
82,83
Factors predicting favourable outcomes in
paediatric epilepsy were similar to those in adults,
including unilobar temporal resection,
20,66,67,81
unifocal
lesion on MRI,
20,66,67,69,73,75,81
complete resection of the lesion
and an active region on EEG,
75
and absence of preoperative
generalised tonic-clonic seizures.
73

There is little research describing long-term (>5 years)
surgical outcomes in children, and very few studies use
modern MRI techniques in the surgical work-up. Hamiwka
and co-workers
84
reported 10-year follow-up data in 38
children with cortical dysplasia or developmental tumours;
there was very little change in outcome at 2 years to
10 years after surgery. 72% of patients with tumours
causing epilepsy were seizure free compared with only
32% of those with cortical dysplasia. Freedom from
seizures was predicted by complete resection of lesions,
and no patient with an incomplete resection of a lesion
was seizure free. However, this study used only 03 tesla
MRI in some patients and therefore might have missed
some pathology. Similarly, Kloss and colleagues
85
reported
68 children with focal cortical dysplasia at 310 years
follow-up. Of these children, 34 were seizure free at 2 years
follow-up, and remained stable at 10 years after surgery.
Again, complete resection of the lesion was the best
predictor of seizure freedom. Mittal and co-workers
74

studied 109 children with surgical treatment for intractable
temporal lobe epilepsy with a mean follow-up of 109 years
(range 520 years), and reported that 82% of patients were
seizure free. These recent studies suggest that, similar to
adult studies, seizure-free outcome remains relatively
stable after 12 years.
A higher proportion of children than adults undergo
repeat resection. This scenario is most common after
incomplete resection of an area of cortical dysplasia.
621% of children having surgery to treat epilepsy will
have a second operation, and 3070% of these patients
will be seizure free, which is similar to gures reported
for adults.
70,73,74,76,84,85
Dual pathology
Dual pathology refers to the coexistence of mesial temporal
sclerosis with an additional potentially epileptogenic lesion
identied on neuroimaging. The need to resect both mesial
temporal sclerosis and another potentially epileptogenic
lesion or to dene their mutual and independent
epileptogenicity is controversial. A greater proportion of
children than adults have dual pathology. A reported
24100% of mesial temporal sclerosis specimens from
children have dual pathology, which most commonly
includes cortical dysplasia followed by low-grade tumours
and, less commonly, vascular malformations, perinatal
injury, or infarction.
19,67,69,7276
Duchowny and colleagues
71

reported 31 infants who had surgery when they were
younger than 3 years old; ve had mesial temporal
sclerosis, all with histologically proven dual pathology
(cortical dysplasia or developmental tumour). By
comparison, 4154% of adult temporal lobe resections
involve mesial temporal sclerosis and another lesion,
including cortical dysplasia, vascular malformation, infarct,
or dysembryoplastic neuroepithelial tumour in descending
order of frequency.
4,76,8690
This higher prevalence of dual
pathology in children than in adults raises the hypothesis
that the additional substrate leads to intractable epilepsy
earlier in life (and thus earlier referral to surgery).
In patients who had surgery, 5090% of children
69,70,7276

and 50100% of adults
4,8690
become seizure free,

although
not all reports specied whether both the mesial temporal
structures and the lesion were resected (table 2).
Resection of one or the other might result in recurrence
of epilepsy in the long term, even when assessment at
the time shows that seizures arise in just one area.
8690

The best consensus from these studies is that dual
pathology does not predict a poorer prognosis than
mesial temporal sclerosis alone when and if the
hippocampus and the additional lesion or cortical
dysplasia are both completely resected, and that failure to
resect the co-existent pathology in some patients is the
primary reason that medial temporal resection does not
cure all patients. The gures reported might, however, be
misleading because the numbers of patients with dual
pathology are sometimes very small within a series, the
resection (or its extent) of the lesion and the mesial
temporal sclerosis is not always well specied, and follow-
up is often shorter than needed to observe the usual
decline over time of seizure-free outcome in patients
with dual pathology. In addition, the criteria for seizure
freedom are not uniform and thus it might be di cult to
compare the results from dierent studies.
Hemispherectomy
Hemispherectomy is now a widely accepted procedure
for medically refractory, catastrophic hemispheric
epilepsy. The classic anatomical hemispherectomy
procedure has been abandoned in favour of functional or
modied hemispherectomy to avoid long-term adverse
events, such as cerebral haemosiderosis, progressive
528 http://neurology.thelancet.com Vol 7 June 2008
Review
neurological decit, or death. Variations of the functional
hemispherectomy include peri-insular hemispherectomy,
modied lateral hemispherectomy, and vertical
parasaggital hemispherectomy. There are no data on the
long-term sequelae or comparisons of these alternatives.
Most studies reporting outcomes of hemispherectomies
are in children, because catastrophic epilepsy is more
commonly related to causes seen in paediatric patients
and morbidity is lower in children than in adults because
of plasticity of the developing brain. The only published
adult series reported seizure freedom in ve of nine
patients.
91
The causes of epilepsy in this study included
birth trauma, encephalitis, gliomas, and vascular
malformation.
The e cacy of hemispherectomy procedures in
children has been established, with recent studies
showing seizure freedom in 4379% of patients.
20,71,9299

Incomplete disconnection and cortical dysplasia
(including hemimegalencephaly) confer a poorer
prognosis. The most common indications for this surgery
are diuse cortical dysplasia, Rasmussens encephalitis,
Sturge-Weber syndrome, and ischaemia or infarction.
The best outcomes were reported for Rasmussens
encephalitis and Sturge-Weber syndrome and the worst
were seen in cortical dysplasia, probably because of the
more restricted nature of the former, and the likelihood
of diuse involvement bilaterally in cortical dysplasia.
9299
Corpus callosotomy
Corpus callosotomy is a palliative disconnection procedure
in which the corpus callosum is sectioned to prevent
interhemispheric propagation of epileptic discharges and
generalisation of seizure activity. E cacy of the procedure
for the targeted generalised seizure types is impressive,
with averaged reductions of 80% in drop attacks,
generalised tonic-clonic seizures, and generalised tonic
seizures in 80% of patients, and 50% reduction in complex
partial seizures, myoclonic seizures, and absence seizures
in both adults and children. Some evidence suggests a
better response in children than in adults and
improvements persist over time.
100

Most series include total or anterior callosotomies.
Disconnection of the anterior section (commonly two-
thirds to four-fths) decreases the risk of acute
disconnection syndrome (mutism, hemiataxia, alexia)
and postoperative morbidity, while providing the desired
seizure eects in 50% of patients. Completion of anterior
section can improve results and is done as a second stage
if needed.
Studies reporting seizure outcome of corpus callosum
sections are variable in terms of the surgical procedure
(anterior vs complete section), seizure types targeted, and
criteria for seizure outcome, thus rendering comparisons
between studies and between outcomes in children and
adults di cult.
In adults, about 4585% of patients with drop attacks
beneted from anterior or complete corpus callosotomy
with a 5090% reduction in seizures, whereas about
4090% had a 5090% reduction in generalised tonic-
clonic seizures. Improvements in seizure outcome were
associated with extent of section in most studies.
Although callosal section is most eective for atonic
seizures, followed by generalised tonic and tonic-clonic
seizures, some patients with atypical absence and
myoclonic seizures can benet from this procedure.
Partial seizures are not a prime indication and are
substantially (>50%) reduced in only a few patients
(30%).
101110

Most outcomes in paediatric studies are reported in
terms of percentage reduction in seizures, with a 50%
decrease in seizures thought to be a good result (akin to
drug trials, rather than other surgical series). Wong and
co-workers
106
reported a 50% or greater reduction in
seizures in 73% of 153 children (nearly all of whom were
mentally retarded); this comprised a 73% reduction in
atonic seizures, 82% in generalised tonic-clonic seizures,
77% in generalised tonic seizures, 65% in myoclonic
seizures, 62% in complex partial seizures with or without
Age Follow-
up (years)
Number of
patients
Patients with MTS+/
patients with MTS
Proportion seizure free after surgery
Benia et al
73
<18 years 2 106 7/23 74% all patients, 88% MTS+ (absence of auras, auras only, or rare
disabling seizures or nocturnal seizures only)
Cascino et al
90
Adult 1 15 3/15 100% (MTS+)
Cossu et al
67
<16 years 2 113 9/11 68%
Duchowny et al
69
211 years 1 16 2/2 69% all patients, 50% MTS+
Li et al
89
873 years 1 64 13/64 100% MTS+ if both hippocampus and lesion resected
Li et al
86
1463 years 1 38 11/15 73% MTS+ if both hippocampus and lesion resected
Mittal et al
74
<19 yrs 520 109 27/49 82% all patients, 74% MTS+
Mohamed et al
72
420 years 17 34 11/14 78% all patients, 90% MTS+
Salanova et al
87
859 years 1 240 37/130 70% MTS+
Terra-Bustamante et al
70
<18 years 1 35 5/14 77% all patients, 80% MTS+
MTS=mesial temporal sclerosis alone. MTS+=dual pathology.
Table 2: Surgical studies reporting dual pathology results
http://neurology.thelancet.com Vol 7 June 2008 529
Review
secondary generalisation, and 59% in atypical absence
seizures. Cukiert
103
described 75 patients with
symptomatic generalised epilepsy (Lennox-Gestaut
syndrome and Lennox-Gestaut-like), 91% of whom had a
greater than 50% reduction in overall seizure frequency
(atonic seizures 92%, generalised tonic-clonic seizures
57%, tonic seizures 51%, myoclonic seizures 27%).
Shimizu and colleagues
95
found that 31 of 35 patients
with total corpus callosotomies were free from atonic
seizures, but only 4 of 6 patients with partial section were
free of atonic seizures. Total callosotomies had better
outcomes than partial callosotomies. Rathore
107
reported
that 9 of 11 patients with total callosotomies had a greater
than 90% reduction in drop attacks compared with only 2
of 6 patients in whom the anterior two-thirds of the
corpus callosum was sectioned. Finally, in a study by
Rahimi,
108
21 of 25 patients had a greater than 75%
reduction in atonic seizures after a total callosotomy,
whereas only 5 of 9 patients with partial callosotomy had
the same result. Despite the dierences in methods of
reporting seizure outcome, we can conclude that more
than 75% of patients will have a greater than 75% decrease
in atonic seizures and that about 5075% of patients will
have a greater than 50% reduction in generalised tonic,
tonic-clonic, and atypical absence seizures.
109,110
Outcome
for myoclonic seizures is variable.
Results are also consistently better for total callosotomies
than for anterior callosotomies in children, but the
procedure can be completed at a second stage if the
desired response is not obtained, which is commonly a
successful strategy as it is in adults.
100

Multiple subpial transection
The rationale for the other common disconnection
procedure, multiple subpial transection, is based on the
horizontal spread of epileptiform activity across
vertically oriented functional units (columns) in the
cortex: by selectively disrupting horizontal connections,
one can theoretically prevent transcortical spread of
seizures and preserve neurological function. This
procedure is usually reserved for those patients in whom
resection of the epileptogenic regions is prevented
because they are in functionally crucial cortex. Multiple
subpial transections are commonly done concomitantly
with some form of cortical resection, a practice that
makes assessment of the outcome of this procedure
problematic.
A meta-analysis
111
that included both adults and children,
with an age range at surgery from 1 to 75 years (mean
26 years), showed a greater than 95% reduction in seizure
frequency in 87% of patients for generalised seizures and
68% for partial seizures after multiple subpial transection
and resection, compared with 71% for generalised seizures
and 62% for partial seizures in patients after transections
alone. Factors predicting better seizure outcome included
younger age at onset of epilepsy, duration of epilepsy of
less than 10 years, and developmental origins or tumour
and perinatal injury as causes. Subsequent to this meta-
analysis, Blount and colleagues
112
reported a series of 30
paediatric patients of whom 87% had both subpial
transections and resection and 13% had transections alone;
46% of patients had a seizure-free outcome.
Multiple subpial transection has been recommended
for acquired epileptic aphasia (Landau-Klener
syndrome; LKS),
113115
in which seizures are variably
present and are easily controlled by antiepileptic drugs in
most cases. Blount and colleagues series included four
patients who had multiple transections for LKS, but only
one had a signicant improvement in language. However,
multiple subpial transection has been helpful for the
treatment of language disturbance in other studies:
Morrell described the results of 14 children with unilateral
multiple subpial transections for LKS:
114
seven children
had full recovery of language, with another four showing
substantial improvement, and 11 were seizure free;
patients with continued seizures also had poor language
outcomes. Irwin and co-workers
115
described improvement
of language in all their patients who were free of seizures
or who had substantial seizure reduction after multiple
subpial transections.
The durability of e cacy of multiple subpial
transections caused concern in an adult series,
116
but
there are few data on this in children or in patients with
LKS.
Neurological outcomes
Outcome in adults
After anterior mesial temporal lobectomies, 044% of
patients had partial hemianopsia, aphasia, motor decit,
sensory decit, or cranial nerve palsy.
2,22,30,35,39,61
Older
reports include 25% incidence of hemiparesis; however,
this was not observed in recent studies, which might
reect renement of selection of patients, modern
neuroimaging techniques, and improvement in operative
techniques and technology. In contrast to the high
morbidity reported in older studies, more recent work
shows that less than 10% of patients have postoperative
occurrence of new motor, visual, or cognitive decits
after neocortical resection.
2,39,42
In the single report of hemispherectomy in adults, one
of nine patients developed dysphasia (with mixed results
from Wada tests) and one had exacerbation of
hemiparesis.
91
Major decits (ie, hemiparesis, visual eld
decits, and memory decline with relative sparing of
language) were noted in 10 of 53 patients given multiple
subpial transections alone and in 37 of 156 patients given
transections with resection.
111
Selection bias probably
accounts for these higher rates, because the procedure is
essentially reserved for epileptic regions in functional
areas.
Although transient decits are not uncommon after
corpus callosotomies (especially total one-stage
procedures) in adults (up to a third of patients with
transient akinetic states or disconnection syndromes),
530 http://neurology.thelancet.com Vol 7 June 2008
Review
decits are permanent in only 017%.
101110
The classic
disconnection syndrome (mutism, ataxia, alexia,
hemineglect, gait apraxia, urinary incontinence) develops
mainly after total callosotomy, and improves with time.
The more severe alien-hand syndrome is unpredictable,
disabling, and rare. Less severe forms of disconnection
revealed with formal testing are rarely noticeable in daily
function as long as vision is preserved in both visual
elds. Language impairments (dyslexia, dysgraphia,
dysphasia) are associated with crossed dominance (eg,
right-handedness and right hemispheric dominance for
language) and might represent a contraindication to this
procedure.
100
Improvements in attention accompany
improvements in generalised seizures in some
studies.
103,105
Outcome in children
The incidence and localisation of postoperative decits
in children also varies with the procedure. The
developing brain possesses considerable functional
plasticity, and, therefore, milder lasting impairments
might be anticipated for children than for adults.
However, infants have small total blood volumes and
are therefore at increased risk of perioperative
complications.
After focal resection, 010% of patients have permanent
sequelae including hemiplegia, homonymous
hemianopsia, quandrantopsia, dysphasia, and decreased
verbal memory. The decit depended on the area resected,
and most were anticipated.
19,20,67,70,73,76,78,81
After hemispherectomy, hemiparesis worsened in a
few patients and improved in others.
93,97
Most patients
remained ambulatory, with useful proximal arm function.
Late shunts were required in 833% of patients.
93,9598,117
Mortality
Outcome in adults
No deaths have been reported perioperatively or from
complications of surgery, except for one death during a
corpus callosotomy of which details were not given.
105

Death after surgery was most common in individuals
with continued seizures; there seems to be a decrease in
relative death risk with surgery. The standard mortality
ratio is high in poorly controlled epilepsy because of
seizure-related trauma, status epilepticus, sudden
unexplained death in epilepsy, and suicide, and might
also be related to the underlying causes of epilepsy.
Mortality in patients who are seizure free after surgery
approaches that in the general population.
34,118,119
Outcome in children
Mortality related to surgery in children, including early
postoperative deaths (due to infections, hydrocephalus,
dehydration, haemorrhage, allergic reactions) and late
postoperative deaths (unexplained or related to
seizures),
20,71,74,106,120
is estimated at 02%, which is higher
than in adults.
Cognitive outcome
Outcome in adults
Most cognitive changes after epilepsy surgery arise in
patients who have anterior temporal lobectomies. The
methods and timing of neuropsychological assessments
documenting these changes are heterogeneous. Most
studies describe signicant decline in verbal memory
after 1950% of dominant temporal resections. This
decline is related to intact preoperative memory, intact
memory performance on the Wada test after injection
contralateral to the seizure focus, an MRI lesion other
than mesial temporal sclerosis, absence of ipsilateral
hippocampal atrophy on preoperative MRI, or other
evidence of preoperative preserved function in the lobe to
be resected (table 3).
121129
Some studies report improvements in verbal memory
and full-scale IQ after resection of the non-dominant
temporal lobe;
125
however, the degree of contribution of
the retest eect and the longevity of these ndings is
unclear.
22,36,128
Performance might be improved once the
deleterious eects of ongoing seizures are gone. A lower
incidence of subjective reports of memory decline (in the
presence of objective memory decline) was observed in
patients with excellent seizure outcome.
126,130
Long-term
studies (with greater than 5 years follow-up) suggest
that, although memory decits develop early after
surgery, the degree of decline stabilises after
12 years.
121,122,124,126,127
Changes in language have not been
reported consistently, and this is probably a result of
extensive pre-resection mapping.
Outcome in children
Between 40% and 50% of children with epilepsy have
high rates of comorbid learning disabilities,
developmental delay, psychiatric and behavioural
di culties, and psychosocial problems. These comorbid-
ities are inuenced by the underlying substrates of the
epilepsy, eects of antiepileptic drugs on the developing
brain, social stigma, and deleterious eects of ongoing
seizures. Therefore, if surgery prevents or even reduces
the severity of seizures, it should improve these
comorbidities.
Cognitive impairment and developmental delay are
more common in children with epilepsy with an earlier
age at onset and more frequent seizures.
131,132
Up to 61%
of patients with intractable epilepsy have mental
retardation,
133
and children with mental retardation or
cognitive delay make up a large proportion of surgery
candidates. Although specic causes of epilepsy might
predict a rapid and severe course, frequent seizure
activity also contributes to developmental stagnation or
decline.
The most convincing evidence of the benecial eect of
surgery on developmental outcome is from studies after
surgery in infants and from hemispherectomy series.
Most patients presented with early catastrophic epilepsy
or progressive hemispheric disorders such as Rasmussens
http://neurology.thelancet.com Vol 7 June 2008 531
Review
encephalitis or Sturge-Weber syndrome. Loddenkemper
and colleagues
133
saw improvements in developmental
quotients in 17 of 24 infants (<3 years of age at surgery)
after surgery for intractable seizures. Jonas and co-
workers
120
reported developmental improvements in 57%
of 115 patients after hemispherectomy. Other studies also
document postoperative improvements,
134,135
whereas some
mainly report a lack of developmental deterioration.
65,71,96,98

Verbal abilities and social or communication skills are
usually preserved regardless of laterality of surgery,
93,96,97,120,122

but there is less impressive improvement in verbal abilities
after left hemispherectomies.
79
Longer duration of epilepsy
correlates negatively with developmental and behavioural
outcomes,
93,96,97,120,122
whereas earlier age at surgery, higher
presurgical IQ, and seizure freedom were associated with
better outcomes.
97,98,120,133,134
In 2005, Freitag and Tuxhorn
79
published results from
50 preschool children (ages 37 years) with both
presurgical and postsurgical developmental assessments;
41 patients showed stable trajectories of development
and three showed gains of 15 IQ points or more at 1 year
after resective epilepsy surgery. At 23 years follow-up,
29 of 40 patients were stable and 8 of 40 had IQ gains of
15 points or more. A shorter duration of epilepsy was
the one predictive factor for cognitive improvement.
This study not only corroborated the trends in infants
but also suggested that developmental gains continue
and might not be fully appreciated for 23 years after
surgery.
Most studies of developmental and cognitive results of
medial temporal resections in children suggest a lack of
signicant change in IQ or verbal memory. Westerveld
and colleagues
136
found improvements in non-verbal
functioning after temporal lobectomy in children. Risk
factors for decline in verbal memory included older age
at surgery and the presence of a structural lesion other
than mesial temporal sclerosis. Other studies reported
similar cognitive outcomes and predictors.
137142
Seizure-
free outcome is not always clearly related to cognitive
outcome. Data on improvements or declines in IQ or
memory changes are conicting but in view of the
expected declines in memory or cognition with poorly
controlled seizures, an absence of decline could be
thought of as a measure of improvement.
Follow-up Number of
patients
Cognitive assessment Results
Alpherts
et al
22
6 years 71 Dutch translation of the WAIS RTL surgery: +29 VIQ points, +77 PIQ points
LTL surgery: +36 VIQ points, +103 PIQ points
Slightly larger increase in FSIQ and PIQ in seizure-free patients
Alpherts
et al
121
6 years 85 15 words test RTL surgery: no change
LTL surgery: ongoing decline for consolidation and acquisition of verbal material
MTS did worse than non-MTS, independent of seizure freedom
Chelune
et al
122
>6 months 96 WAIS-R, WMS-R RTL surgery: mild decline in verbal memory
LTL surgery: decreased general and verbal memory, positive changes in FSIQ
Engman
et al
123
2 years 25 WAIS-R, Cronholm-Molander memory test, Rey-Osterrieth
complex gure memory test
Individual increases and decreases in PIQ and verbal memory at 2 years but return to
baseline by 10 years
Helmstaedter
et al
124
1 year and
210 years
147 VLMT, DCS-R, letter-cancellation test, German intelligence
test
Medical subjects: decreased verbal memory in 29%, decreased gural memory in 36%
RTL surgery: decreased verbal memory in 24%, decreased gural memory in 34%
LTL surgery: decreased verbal memory in 47%, decreased gural memory in 28%
No dierence for non-memory functions and stabilisation of memory postsurgically
compared with medical therapy alone
Hermann
et al
125
>6 months 57 CVLT RTL surgery: increased recall of verbal memory
LTL surgery: decreased recall of verbal memory
Langtt
et al
126
2 years and
5 years
138 Long delay free recall (CVLT) 37% with memory decline of >1 SD
Martin et al
127
>6 months 101 WAIS-R, logical memory test (WMS and CVLT), BNT, visual
reproduction immediate and delayed recall (WMS)
RTL surgery: decreased immediate and delayed episodic prose recall in 33%, although
33% also had increased delayed prose recall
LTL surgery: decreased verbal semantic and episodic memory tasks in 2550%
Rausch et al
128
9 years 44 WAIS, WMS mental-control, associative-learning, logical
prose (immediate and retention), and visual reproduction
(immediate and retention) subtests, trail-making A and B,
Rey-Osterrieth complex gure memory test
RTL surgery: no change over controls
LTL surgery: decreased verbal memory, which continued to decline in the long term
Sanyal et al
36
1 year 25 AIIMS comprehensive neuropsychological battery (in Hindi) RTL surgery: seven of nine with good seizure outcome had >20% improvement in
memory and IQ
LTL surgery: no change
Stroup et al
129
>6 months 132 Long delay free recall (CVLT), logical memory immediate
and delayed recall tests (WMS-R)
38% decline on one or both verbal memory tests; worse with dominant hemisphere
AIIMS=All India Institute of Medical Sciences. BNT=Boston naming test. CVLT=California verbal learning test. DCS-R=Diagnostikum fur Zerebralschadigung revised. FSIQ=full-scale intelligence quotient. LTL=left
temporal lobectomy. MTS=mesial temporal sclerosis. PIQ=performance intelligence quotient. RTL=right temporal lobectomy. VIQ=verbal intelligence quotient. VLMT=verbaler Lern and Merkfahigkeits test.
WAIS=Wechsler adult intelligence scale. WAIS-R=WAIS revised. WMS=Weschler memory scale. WMS-R=WMS revised.
Table 3: Cognitive changes after temporal lobectomy in adults
532 http://neurology.thelancet.com Vol 7 June 2008
Review
Psychiatric outcomes
Outcome in adults
Psychiatric disorders are present in up to 50% of patients
with epilepsy; the most common in adults are aective
disorders such as depression, mania, and anxiety, and
some patients have acute psychosis.
143147
Some studies,
usually in patients with anterior temporal lobectomy,
have tried to dene the eect of surgery on psychiatric
disturbances and the risk factors for sequelae, but most
did not include presurgical and postsurgical assessments
and so their results might not be valid.
A large German longitudinal study of 147 surgically
treated patients and 102 medically treated patients with
temporal lobe epilepsy found depression in only 21% of
surgically treated patients compared with 43% of
medically treated patients (using the Beck depression
inventory) and, more importantly, in 12% of seizure-free
patients compared with 44% of those with continuing
seizures across both medical and surgical groups.
124
The largest prospective study to date, a multicentre
study,
148
reported 360 patients (89% of whom had
temporal lobectomies) who had presurgical and repeated
postsurgical psychiatric assessments (Beck depression
inventory, Beck anxiety inventory, composite international
diagnostic interview). Overall, depression and anxiety
were reported in 221% and 247% of patients,
respectively, declining gradually over 2 years to 114%
and 123%, respectively. At 24 months, fewer patients
who were seizure free had moderate to severe depression
(82%) and anxiety (82%) than did patients who were
not seizure free (176% and 147%, respectively). Many
recent studies (although not all) indicate that better
seizure outcomes predict improvements in psychiatric
status.
33,124,135,143,144,149,150
In addition, numerous reports show
that presurgical presence of psychiatric disorders is a
signicant risk factor for psychiatric morbidity
postsurgically.
33,144,145,150,151
Other variables (laterality of
surgery, localisation of seizure focus, age at time of
surgery, and continued auras) are not consistently
associated with psychiatric sequelae.
After surgery 430% of patients develop new aective
disorders. 15% develop psychosis, although reports
from the past decade show lower incidences than earlier
studies. The wide range in reported incidence seems to
depend on the time interval from surgery; psychiatric
symptoms seem to peak at 23 months, with gradual
improvements by 12 years.
143,144,148,151153
Risk factors for
and the mechanisms of development of de-novo psychosis
after surgery are unknown.
Outcome in children
Common psychiatric and behavioural comorbidities of
epilepsy in children include depression, anxiety, attention
decit hyperactivity disorder, conduct problems, and
aggression; these might be present in up to half of
children and adolescents with epilepsy.
154,155
The few data
available suggest that children with epilepsy are nearly
ve times more likely to have behavioural problems than
healthy children or children with other chronic
illnesses.
156
Lendt
154
found that in a study of 28 children,
the proportion with borderline and signicant
behavioural problems presurgically decreased to 32%
postsurgically; overall scores improved compared with
no change in the control group of patients treated with
drugs. Seizure freedom predicted good behavioural
outcome. Cendes and colleagues
109
reported that 81% of
34 patients had a signicant reduction in aggression,
hyperactivity, and attention di culties after corpus
callosotomy.
Heath-related quality of life
Outcome in adults
The real eects of any intervention are seen in the
patients overall health goals. Health-related quality of
life (HRQOL) includes multiple domains (physical,
psychological, social, vocational, and economic).
Although there is much published on this measure, the
heterogeneity of HRQOL instruments and the timing of
measurements limit comparisons. The most
comprehensive and applicable inventory is the quality of
life in epilepsy inventory-89 (QOLIE-89) developed from
the epilepsy surgery inventory-55 (ESI-55); both have
been validated in large series of patients with epilepsy.
157159

These inventories were developed in the USA, however,
and are not universally adopted. Others have been used
internationally but there is minimal consistency.
Numerous retrospective studies, case series, and cohort
studies comparing patients after surgery with those
awaiting surgery or medically managed patients
consistently show better HRQOL, satisfaction, overall
psychosocial well-being, and functional status with
surgery.
23,27,28,31,124,156,160,161
Although these studies provide
valuable information, the lack of preoperative
comparisons and absence of true control populations in
most limits their validity.
In the only randomised, controlled trial of temporal lobe
surgery for epilepsy,
39
the surgical group (N=40; 58%
without seizures that impaired consciousness) consistently
scored higher on the QOLIE-89 than the medical group
(N=40), as early as 3 months after surgery and continuing
to 12 months, but both groups reported improvements in
HRQOL, and the eect of seizure freedom was not
reported.
In a large prospective surgical series (396 patients) in
which the QOLIE-89 was used before surgery and up to
5 years after surgery, the most substantial improvement
in HRQOL was immediately after surgery in all patients,
but further improvements were seen in the seizure-free
group. This eect stabilised at 2 years after surgery and
was related to duration of seizure freedom. In the group
with best seizure outcome at 5 years after surgery,
HRQOL was comparable to that in the general population
in all domains of the SF-36 (a 36-item short-form health
survey that comprises the generic core of the QOLIE-89)
http://neurology.thelancet.com Vol 7 June 2008 533
Review
except for social functioning.
162
Another prospective study
using the ESI-55 to assess 72 patients corroborated these
ndings but noted improvements in patients who were
seizure free and in patients with a reduction in seizures
of 90% or more; these improvements took up to 2 years
after surgery to appear.
163
Helmstaedter
124
reported a signicant dierence in
QOLIE-10 scores in medically treated (N=102) and
surgically treated (N=147) patients (severely impaired
quality of life in 33% and 10%, respectively; p<00001)
and in those who were seizure free and those with
continued seizures (3% compared with 31%; p<0001).
Recently, Tanriverdi and colleagues
164
found improved
quality of life (on QOLIE-10) in 23 patients with surgically
treated extratemporal epilepsy at both 6 months and
2 years after surgery, with the greatest improvements in
those patients who were seizure free.
Another method of determining well-being is to assess
the patients perceived eect of surgery or satisfaction.
Chin and co-workers
165
found that of 396 patients, 80%
would make the same decision (to have surgery) if given
the choice again, and 9192% reported a strong or very
strong impact of surgery (inuenced by seizure freedom
and gainful employment). Dupont and colleagues
reported a similar proportion of satisfaction among
patients treated with surgery.
27
Studies of the possible benets of epilepsy surgery on
vocational status, however, have consistently found only
modest improvements postoperatively, with seizure
freedom being the strongest predictive factor.
27,38,165
These
observations might reect the predisposing eect of
longstanding epilepsy on education and psychosocial
status, and lend weight to the need for postoperative
vocational rehabilitation.
Outcome in children
There has been a recent increase in interest in the
measurement and assessment of HRQOL in children
and adolescents with chronic epilepsy. Low HRQOL
results from several inter-related factors.
166
Severity and
duration of epilepsy, comorbid impairments (cognitive,
behavioural, neurological), number of antiepileptic
drugs, and toxic eects diminish HRQOL in children
and adolescents. The eect on psychosocial functioning
continues into adult life.
166171
As the duration and severity
of epilepsy are among the most important determinants
of psychosocial well-being for both the child and their
family, HRQOL might improve postoperatively with
seizure freedom; establishing this, however, is di cult.
Although measurements of HRQOL for children have
been developed, few have been validated, and
heterogeneity among centres hampers comparison. In
addition to poorly applied or available measurements,
many studies are cross-sectional or retrospective.
In a prospective longitudinal study of 21 children
undergoing focal resections and hemispherectomies to
treat epilepsy, scores of self-worth and competence
improved by 2 years postoperatively, and most
improvements were seen in the rst 6 months, as in
adults. Parental perceptions of HRQOL were related to
those of their children. The scales used were the how-are-
you inventory, the Hague seizure severity scale, and the
Hague restrictions in epilepsy scale.
172
Other recent
retrospective or cross-sectional studies found similar
improvements irrespective of the type of resection.
154,173175
By contrast, Smith and colleagues
141
found no change in
HRQOL when measured preoperatively and 1 year later
(with the Aachenbach child behaviour checklist and the
Pier-Harris scales) compared with children with
intractable epilepsy not treated with surgery. The generic
nature of the scales and the short period of follow-up are
limitations of this study.
Maehara and co-workers
92
found improvements in daily
function and overall parental satisfaction by use of
questionnaires in 62% and 83% of children, respectively,
after corpus callosotomy. The most notable improvements
were in hyperactivity, emotional well-being, and
socialisation. A few parents also noted depression and
stammering as negative sequelae. Improvements were
most common in those with better seizure outcome and
in young patients. Other studies examining HRQOL in
children after corpus callosotomy found similar
improvements.
110,176,177
Mizrahi and colleagues
178
examined the eect of a delay
in temporal lobe surgery on psychosocial functioning by
comparing patients who had surgery at dierent ages.
Despite similar seizure outcomes, many patients who
had surgery later in life had a higher incidence of
psychosocial, behavioural, and educational di culties
than those who had earlier surgery. This nding is
important because it raises the question of whether
epilepsy surgery should be done early in children to
ameliorate these potential psychosocial decits.
Conclusions
The low morbidity and benet of epilepsy surgery for
intractable seizures are well established for adults with
medically refractory epilepsy. There is increasing interest
in more global outcomes of surgery, which might lead to
substantial improvements for patients. Seizure freedom
seems to be the strongest and most consistent predictor
for improvements in HRQOL and patients perceived
satisfaction, and therefore we should continue to aim for
this goal and pursue procedures that allow seizures to be
stopped whenever possible.
In carefully selected children, surgery is now also
established as an eective and safe treatment for
intractable epilepsy. In addition to signicant reduction
or cessation of seizures, benets of epilepsy surgery in
children include improved development, psychosocial
functioning, and overall HRQOL. Incomplete data
regarding these ancillary outcomes and the issue of when
surgery is most benecial in the developing brain
demand further research.
534 http://neurology.thelancet.com Vol 7 June 2008
Review
Contributors
Both authors contributed equally to all aspects of the preparation of this
Review.
Conicts of interest
We have no conicts of interest.
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Search strategy and selection criteria
We did a comprehensive literature search of MEDLINE and the
Cochrane database with the key phrases outcome of epilepsy
surgery, outcome of paediatric epilepsy surgery, epilepsy
surgery, paediatric epilepsy surgery, resection, multiple
subpial transections, corpus callosotomy,
hemispherectomies, epilepsy surgery and quality of life,
epilepsy and quality of life, epilepsy surgery and
psychiatric disorders, paediatric epilepsy surgery and
quality of life, paediatric epilepsy and quality of life, and
paediatric epilepsy and psychiatric disorders. Other
references were also obtained from references of published
papers. Papers were included if they met the following criteria:
publication from 1990 to March 2008, all patients had MRI as
part of the surgical work-up, all patients had at least 1 year
postsurgical follow-up, and presurgical and postsurgical
information for specic outcomes were available. Papers with
overlapping populations of patients were excluded when the
information was available. The papers were separated into
adult (>18 years) or paediatric populations, or mixed.
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